Animal Model and Cell Isolation Core

动物模型和细胞分离核心

• 批准号: 10397512
• 负责人: COLLEEN MARIE CRONIGER
• 金额: $ 18.08万
• 依托单位: CLEVELAND CLINIC LERNER COM-CWRU
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-05-01 至 2026-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10397512
• 关键词: Acute; Acute Hepatitis; Alcohols; Animal Model; Animals; Back; Biological Assay; Body Weight; Cell Separation; Cell model; Cells; Chronic; Complex; Consult; Consultations; Cost Savings; Data; Data Analyses; Databases; Development; Eating; Endothelial Cells; Ensure; Equipment and supply inventories; Ethanol; Experimental Designs; Exposure to; Fibrosis; Funding; Genetic; Genetic Models; Goals; Harvest; Hepatic; Hepatic Stellate Cell; Hepatocyte; Human Resources; Immune; In Vitro; Injury; International; Knock-out; Laboratories; Lead; Liver; Maintenance; Metabolic; Modeling; Molecular; Molecular Target; Mus; National Institute on Alcohol Abuse and Alcoholism; Ohio; Pathogenesis; Pilot Projects; Population; Primary Cell Cultures; Procedures; Process; Protocols documentation; Quality Control; Rattus; Research; Research Personnel; Research Project Grants; Research Support; Resources; Rodent; Sampling; Sorting - Cell Movement; Source; Standardization; System; Techniques; Testing; Therapeutic Intervention; Tissue Sample; Tissues; alcohol exposure; alcohol research; alcohol response; animal breeding; biobank; body system; clinically relevant; design; diet-induced obesity; efficacious treatment; experience; experimental study; in vivo Model; innovation; macrophage; member; mouse model; novel; novel therapeutic intervention; response; sound; targeted treatment; tissue injury; treatment strategy

ABSTRACT The overall goal of the Northern Ohio Alcohol Center (NOAC) is to identify specific molecular targets of ethanol- induced damage, as well as understand the complex adaptive and maladaptive responses of cells and systems to that injury. This information will enable us to 1) target therapeutic interventions that will either slow and/or reverse the progression of alcohol-induced tissue injury and 2) develop specific assays that can assess the efficacy of novel therapeutic strategies in relevant clinical populations. NOAC brings together an outstanding team of interdisciplinary investigators. Progress by these investigators into the mechanisms of ethanol-induced tissue injury is supported by the Animal Models and Cell Isolation Core (Animal/Cell Core). The use of standardized protocols for in vivo models of acute and chronic ethanol exposure to rodents, as well as the use of in vitro primary cell cultures isolated from ethanol-exposed animals, is critical to understanding the molecular mechanisms for the pathogenesis of alcohol-induced tissue injury. The purpose of the Animal/Cell Core is to provide expertise in the design and implementation of experiments investigating alcohol-induced tissue injury, as well as standardized protocols and centralized facilities for the exposure of rodents to ethanol, as well as isolation of hepatocytes and non-parenchymal cells from the liver. The Core provides support for Research Components and Pilot Projects supported by NOAC, as well as additional projects funded by NIAAA and other sources to local investigators, as well as investigators nationally and internationally. Personnel experienced in working with rat and murine models of acute and chronic ethanol exposure, as well as isolating parenchymal and non-parenchymal cells from rodents, staff the Animal/Cell Core. The proposed Research Components and Pilot Projects will make use of the Animal/Cell Core. The major goal of the Animal/Cell Core will be to make tissue and cellular samples from control and ethanol-exposed animals available to members of NOAC. The procedures involved are complex and expensive; the availability of centralized facilities will allow rapid access of investigators in NOAC, as well as investigators new to alcohol research, to the tissues and cells needed to test novel and innovative hypotheses without the delay of each PI developing these techniques in each of their own laboratories. The Animal/Cell Core also maintains an extensive biorepository of tissues and cells from ethanol-exposed mice and rats. This biorepository allows for considerable cost savings that result from the shared use of samples between the different members of NOAC. Importantly, the shared use of samples is also leveraged to integrate data from multiple investigators to better understand interactions between cells, tissues and systems in response to ethanol. The combination of our outstanding investigative team and excellent Core resources will lead to key discoveries on mechanisms of alcohol-induced tissue injury and lead to the development of efficacious treatment strategies.

抽象的 北俄亥俄州酒精中心 (NOAC) 的总体目标是确定乙醇的特定分子靶点 诱导的损伤，以及了解细胞和系统复杂的适应性和适应不良反应 到那个伤害。这些信息将使我们能够 1) 有针对性的治疗干预措施，这些干预措施将减缓和/或 逆转酒精引起的组织损伤的进展，2) 开发可以评估酒精引起的组织损伤的特定测定法 新治疗策略在相关临床人群中的疗效。 NOAC汇聚了杰出的 跨学科研究人员团队。这些研究人员在乙醇诱导的机制方面取得的进展 组织损伤由动物模型和细胞分离核心（动物/细胞核心）支持。使用 啮齿动物急性和慢性乙醇暴露体内模型的标准化方案，以及使用 从暴露于乙醇的动物中分离出的体外原代细胞培养物，对于理解分子生物学至关重要 酒精引起的组织损伤的发病机制。动物/细胞核心的目的是 提供设计和实施研究酒精引起的组织损伤的实验的专业知识， 以及啮齿动物接触乙醇的标准化协议和集中设施，以及 从肝脏中分离肝细胞和非实质细胞。核心为研究提供支持 由 NOAC 支持的组件和试点项目，以及由 NIAAA 和其他机构资助的其他项目 当地调查人员以及国内和国际调查人员的信息来源。人员经验丰富 使用急性和慢性乙醇暴露的大鼠和小鼠模型，以及分离实质 和来自啮齿动物的非实质细胞，构成动物/细胞核心。拟议的研究组成部分和 试点项目将利用动物/细胞核心。动物/细胞核心的主要目标是使 NOAC 成员可以获得对照动物和乙醇暴露动物的组织和细胞样本。这 所涉及的程序复杂且昂贵；集中设施的可用性将允许快速访问 NOAC 的研究人员以及刚接触酒精研究的研究人员，了解酒精研究所需的组织和细胞 测试新颖和创新的假设，而不会延迟每个 PI 在其各自的领域中开发这些技术 自己的实验室。动物/细胞核心还维护着一个广泛的组织和细胞生物储存库 暴露于乙醇的小鼠和大鼠。该生物样本库可以节省大量成本，因为 NOAC 不同成员之间共享样本。重要的是，样品的共享使用也 用于整合多个研究人员的数据，以更好地了解细胞、组织之间的相互作用 和响应乙醇的系统。我们优秀的调查团队和优秀的核心的结合 资源将导致酒精引起的组织损伤机制的重大发现，并导致 制定有效的治疗策略。